p53 mutations in solar keratoses

To understand how sunlight acts as a carcinogen, the authors analyzed p53 gene mutations including point mutation, loss of heterozygosity (LOH), and overexpression in solar keratoses. Exons 4 to 9 of the p53 gene were amplified by polymerase chain reaction (PCR) and directly sequenced. To determine allelic loss of p53, the region containing polymorphic codon 72 was amplified and digested with BstUI restriction nuclease. Overexpression of p53 protein was detected in paraffin section using mouse monoclonal antibody (PAb 1801). Point mutations of the p53 gene were detected in 7 (28%) of 25 solar keratoses and predominant in pyrimidines (86%). Loss of allele was found in 29% of informative samples. Seven (28%) cases showed immunopositivity; four cases had point mutation, but three cases did not. Two cases with point mutation were immunonegative. Characteristically point mutations, LOH and immunopositivity of p53 were seen predominantly as bowenoid and hypertrophic type lesion. These results suggest that sunlight can cause mutations of p53 gene and that p53 gene mutations may play an important role in skin carcinogenesis.